ILSI Research Foundation

Workshop: Evaluating the Human Relevance of Modes of Action in Animals

This half-day workshop presents a systematic approach to characterizing the mode(s) of action (MOA) of toxicants and will give participants “hands-on” experience in the application of a framework for evaluating the relevance of an animal mode of action in assessing human risk. Frameworks for characterizing MOA data for carcinogens and analyzing its human relevance have been developed over the past decade and cited in various national and international risk assessment guidelines.  More recently, these concepts have been extended to non-cancer endpoints including reproductive, developmental, neurologic and other toxic effects. The evaluation of mode of action is becoming a routine component of regulatory risk assessments, and an important consideration is always whether the MOA determined in animals can be assumed to be directly applicable for humans. This workshop will demonstrate the use of an MOA human relevance framework, through a combination of lecture and interactive case studies with group participation. Opening tutorial presentations will introduce workshop participants to basic concepts and walk them through a model case study.  This leads into a series of facilitated interactive case studies in which participants, working in small groups, analyze examples of varying complexity, drawn from recent peer reviewed publications involving “real world” chemicals. In the case studies, participants will systematically examine the sufficiency of evidence for establishing an MOA and its human relevance.  The cases selected illustrate the comparability between MOA analysis for cancer and non-cancer endpoints, the problem of data-poor situations that preclude a full MOA human relevance analysis, and differences in animal-human MOA analysis based on differences in developmental stage.  The objective of the case studies is to show clearly how the framework analysis is done, to illustrate the importance of a systematic evaluation of the available data, and to provide course participants with the tools and confidence to begin applying the MOA/human relevance framework in their own work.  The speaker/facilitators for this workshop - Dr. Vicki Dellarco, Dr. Penny Fenner-Crisp, and Ms. Bette Meek - have been leaders in the development of MOA human relevance analysis and have extensive experience in its practical use.